The major objective of this research is to gain insights into the biochemical mechanisms involved in the induction, mediation and maintenance of long-term sensitization as well as the interrelationship between the short- and long-term forms of this simple example of nonassociative learning. To address these issues we will utilize the tail-siphon withdrawal reflex in Aplysia. Key components of this reflex and its plasticity are the large homogeneous clusters of bilaterally symmetrical sensory neurons in the pleural ganglia. Our specific focus will be on the identif- ication and characterization of proteins and their regulation in sensory neurons, an understanding of which is a prerequisite to elucidate cellular mechanisms of learning and memory in this model system. The proposal has four specific aims. First, identify proteins whose synthesis and/or phosphorylation are altered by sensitization training and by treatments that mimic the effects of sensitization training. Although we will be screening for changes of all proteins, we will pay particular attention to proteins involved in the metabolism of second messengers. We will try to select, for further study, proteins that are behaviorally relevant. Second, determine the temporal relationship between protein changes and the induction treatments. Third, identify mechanisms that produce changes in the proteins. Fourth, identify functions of proteins altered by induction treatments. research will extensively use quantitative analysis of proteins separated by two dimensional gel electrophoresis and peptide sequencing. This research will provide substantial new insights into the mechanisms for the induction, storage and read-out of a form of long-term memory as well as help address fundamental questions regarding the memory. Moreover, the research will provide general information on the role of specific proteins and second messenger systems in cellular function and plasticity.